ABSTRACT

Most photosensitizers are highly hydrophobic molecules that preferentially accumulate in one or more cellular membranes. Even the photosensitizers that are water soluble still contain hydrophobic cores that tend to bind membranes. Photosensitizers usually target three main organelles: mitochondria, endoplasmic reticulum, and lysosomes (Oleinick et al., 2002). Photosensitizers that are eective in killing cancer cells tend to localize to mitochondria, suggesting that an eective means to kill cells is to deprive them of a primary energy source. Examples of mitochondria-targeted photosensitizers are porphyrins and porphyrin-related macromolecules that are hydrophilic and accumulate in cellular membranes (Roberts and Berns, 1989). Porphyrins are precursors in the biosynthetic pathway to heme, including the endogenous mitochondrial uorescent photosensitizer protoporphyrin IX, which accumulates into mitochondria via the 18 kDa translocator protein in the mitochondrial outer membrane (Anholt et al., 1986). An example of a nonporphyrin mitochondria-targeted photosensitizer is phthalocyanine 4 (Pc 4), which binds preferentially to mitochondria, endoplasmic reticulum, and Golgi complex but not to plasma membrane as assessed by confocal microscopy (Trivedi et al., 2000; Lam et al., 2001).